There has recently been evidence of links between the central nervous system and the immune system. Stressed animals show impairment in several immune parameters and are more likely than control animals to develop cancer when inoculated with an oncogenic virus. Similar derangements in host-defense mechanisms have also been observed with injections of glucocorticoids and lesions in the anterior hypothalamus. The clinical implications of these findings have not been adequately investigated. Epidemiological studies show an increase in morbidity rates following stressful life events such as bereavement and suggest an association between depression, allergy and certain forms of cancer. A number of studies have shown an impairment of different immune parameters following psychosocial stress. Very little research has been done on the immune status of patients with depressive illness. This issue is particularly interesting in view of recent findings in depressed patients of a disturbance in the hypothalamic-pituitary-adrenal axis activity often resulting in the secretion of excessive amount of cortisol, an immunosuppressive hormone. We have recently formulated the hypothesis that depression may be accompanied by an impairment of immune responses that could explain the reported increase in the incidence of infection, allergy and cancer in depressed patients. Preliminary data from our own laboratory indicate a suppression of in vitro lymphocyte mitogenic activity in depressed patients compared to normal controls. This proposal seeks to further explore the possibility of immune dysfunction in patients with depressive illness by giving them a battery of immunological tests, including hypersensitivity skin testing, lymphocyte surface marker analysis with monoclonal antibodies, assessment of in vitro lymphoblast transformations and an assay of natural killer cell activity. Depressed patients will be studied both during the acute phase of depression and following recovery. Comparisons of immune function will also be made between clinical as well as neuroendocrine subtypes of depression. Depressed patients will also be compared to schizophrenic controls, highly stressed but otherwise psychiatrically-well controls and normal controls.